Neutrophil-Derived Heparin-Binding Protein (HBP/CAP37) Deposited on Endothelium Enhances Monocyte Arrest under Flow Conditions

• Published in: The Journal of immunology (1950) Vol. 174; no. 10; pp. 6399 - 6405
• Main Authors: Soehnlein, Oliver, Xie, Xun, Ulbrich, Holger, Kenne, Ellinor, Rotzius, Pierre, Flodgaard, Hans, Eriksson, Einar E, Lindbom, Lennart
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-05-2005
• Subjects: Adjuvants, Immunologic - physiology; Animals; Antimicrobial Cationic Peptides; Blood Proteins - metabolism; Blood Proteins - physiology; Calcium - metabolism; Calcium Signaling - immunology; Carrier Proteins - metabolism; Carrier Proteins - physiology; Cattle; Cell Line; Cell Migration Inhibition; Cytosol - metabolism; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Humans; Intracellular Fluid - metabolism; Macrophage Activation; Medicin och hälsovetenskap; Monocyte Chemoattractant Proteins - metabolism; Monocyte Chemoattractant Proteins - physiology; Monocytes - immunology; Monocytes - metabolism; Monocytes - pathology; Neutrophil Infiltration - immunology; Neutrophils - metabolism; Protein Binding
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.10.6399

In acute inflammation, infiltration of neutrophils often precedes a second phase of monocyte invasion, and data in the literature suggest that neutrophils may directly stimulate mobilization of monocytes via neutrophil granule proteins. In this study, we present a role for neutrophil-derived heparin-binding protein (HBP) in monocyte arrest on endothelium. Adhesion of neutrophils to bovine aorta endothelial cells (ECs) or HUVEC-triggered secretion of HBP and binding of the protein to the EC surface. Blockade of neutrophil adhesion by treatment with a mAb to CD18 greatly reduced accumulation of HBP. In a flow chamber model, immobilized recombinant HBP induced arrest of human monocytes or monocytic Mono Mac 6 (MM6) cells to activated EC or plates coated with recombinant adhesion molecules (E-selectin, P-selectin, VCAM-1). However, immobilized recombinant HBP did not influence arrest of neutrophils or lymphocytes. Treatment of MM6 cells with recombinant HBP evoked a rapid and clear-cut increase in cytosolic free Ca(2+) that was found to be critical for the HBP-induced monocyte arrest inasmuch as pretreatment with the intracellular calcium chelating agent BAPTA-AM abolished the evoked increase in adhesion. Thus, secretion of a neutrophil granule protein, accumulating on the EC surface and promoting arrest of monocytes, could contribute to the recruitment of monocytes at inflammatory loci.